A single-blind ascending dose study was conducted in 5 subjects to determine whether nalmefene glucuronide precipitates withdrawal symptomatology in opiate-(methadone) dependent individuals. If the glucuronide were shown to exert a selective effect on the enteric nervous system without antagonizing central opiate actions, it could be useful in patients requiring high doses of opiates, but who suffer from gastrointestinal side effects (e.g., constipation). However, withdrawal symptoms were induced at relatively low doses (e.g., 1 mg po daily). Thus nalmefene glucuronide does not appear to be useful for constipation associated with the administration of exogenous opiates in opiate-- dependent subjects. It may be useful, however, in patients with constipation who are not opiate-dependent, such as persons suffering from constipation - predominant irritable bowel syndrome.